Biological Evaluation of Garcinia kola Heckel

Garcinia kola belongs to the Garcinia genus of the Clusiaceae family and Malpighiales order. It contains more than 180 members all over the globe. It is found all over Asia and in tropical African countries. In Africa, traditionally, G kola is used to manage and treat cancer, diabetes, malaria, analgesics, hypertension, and other numerous ailments. This review aimed to comprehensively update relevant information regarding the pharmacological potential of Garcinia kola. Electronic databases such as ScienceDirect, PubMed, Wiley, Google Scholar, Hindawi, and Springer extracted valuable information from original scientific research papers. Inclusion Criteria. Antioxidant, antimicrobial, antidiabetic, antibacterial, medications, antiviral, traditional medicine, ethnopharmacology, toxicity, cytotoxic action, chemical composition, mineral elements, GCMS analysis, and any other related phrases were used as filters to find studies. Exclusion Criteria. Data from questionable online sources, as well as thesis reports and review publications, were excluded from this investigation. The investigation revealed that seeds of G. kola are very efficient as antioxidant, antimicrobial, antidiabetic, antihypertension, antianalgesic, and anti-inflammatory. The study also found that too much consumption of the seeds caused low fertility and toxicity. However, the safety and efficacy of G. kola have not been wholly assessed in humans, and further well-designed clinical trials are needed to corroborate preclinical findings. The mechanism of action of the seed extract should be examined. The standard dose and safety of the seed should be established.


Introduction
Traditional medicines produced from plants have become more important as alternative medicines in treating a broad spectrum of ailments, and researchers are continuing to pay attention to the use of plant materials in the treatment of many afflictions [1,2]. e majority of the developing world believes that these plant-based products are safer and more cost-effective [3]. With the emergence of new diseases and microorganism resistance, the usage of these plant products has increased in developed, developing, and underdeveloped countries [4,5]. Ethnopharmacology and medication discovery employing plant-based products are still critical in healthcare delivery worldwide. Garcinia kola is regarded as a miracle plant because every component has medicinal use. e following reviews aimed to update and do a comprehensive review regarding the biological potential of G. kola.
Exclusion criteria: Data from questionable online sources, as well as thesis reports and review publications, were excluded from this investigation.

Taxonomy, Distribution, and Morphology of Garcinia kola.
e Garcinia genus includes Garcinia kola from the Clusiaceae family and Malpighiales order [6]. It contains more than 180 members all over the globe. Synonym names are; Garcinia akawaensis Spirlet, Garcinia giadidii De Wild, and Garcinia bergheana Spirlet. G. kola is a sub-Saharan African forest tree that has been dubbed a "wonder plant" since practically every portion of it has been proven to have medicinal value. It grows natively from Sierra Leone to Southern Nigeria, then on to Zaire and Angola, but it has been widely spread by man and is frequently found growing near communities. It is a tree grown in the Central and West Africa coastal rain forests. It is found all over Asia and in tropical African countries. It reaches a height of about 30 m. e orange-sized fruit is smooth and reddish yellow, with peach-like skin and yellow flesh, and three or four seeds with a brown seed coat. e seed is a nut that may be eaten. e seed coat is dark with branching lines, while the kernels are pale and punctured with resin pockets (Figure 1). Fruits are yellow, reddish, and orange-sized, with a yellow-orange, sometimes reddish pulp. e greenish-white flowers have a reddish indumentum [6].

Biological Evaluation.
Alternative medicine is based on medicinal plants, which has led to the development of many novel pharmaceuticals [8]. More than 80% of medicine was derived from plants in the nineteenth century. e scientific revolution led to the development of the pharmaceutical business, where manufactured pharmaceuticals became more prominent [9].
ere is greater usage of medicinal plants in treating ailments because they are regarded as safe and effective pharmaceuticals, have fewer side effects, and cost less than other drugs [10]. Garcinia kola was subjected to several biological tests (Table 1).

Antioxidant.
e presence of free radicals and reactive oxygen species refers to oxidative stress, which is produced under normal human physiological activity but are harmful when not removed [11]. Kolaviron appears to be as effective as BHA as an in vivo natural antioxidant and an effective hepatoprotective agent in the current study [12]. ese data suggested that G. kola seeds might be beneficial in minimizing the oxidative damage caused by chronic ethanol therapy in the livers of Wistar rats. e phenolic content of the antioxidant was found to be between 10 and 21 mg·g− 1 , and the scavenging was found to be between 26% and 55%, indicating that it will serve as a reservoir of natural antioxidants and be used as food enhancers [13]. Using the radical trapping test and the ion conversion method, we revealed that Ci 50 (65.86-1.17 g/ mL) and the reducing power of the Ferric ion (125.4-4.91 mg/mL) are statistically significant [14]. ere was a substantial increase in total white blood cell count but not in hemoglobin (p > 0.05). ese data suggest that the seeds have immune-stimulatory capabilities, which could support the claims of ethnomedicinal efficacy ( Table 1). All antioxidant biological evaluations carried out were found to exhibit significant activity irrespective of the method (Table 1).

3.4.
Antibacterial. Consistent use of synthetic antibiotics is the leading cause of resistance in bacteria, which can be connected with biological phenomena such as membrane permeability, mutations, physiochemical changes, and efflux dynamics in target microorganisms [15]. In comparison to other microbes, bacterial strains have the genetic potential to rapidly acquire and transfer resistance to routinely used antibiotics [15]. Antibacterial medication resistance is becoming a critical global problem, prompting researchers to look for novel compounds with antibacterial properties and the potential to be used as raw materials in developing new treatments [16]. Some bacterial strains were isolated from tooth caries; therefore, the fraction of ethyl acetate hexane had the highest inhibitory activity against Streptococcus viridans and Streptococcus mutans at 0.33 and 0.33 mg·mL −1 , respectively [17]. It is commonly used to treat toothache and prevent dental cavities, proving the traditional herbalist's claim [17]. e extracts showed an inhibitory effect on the test isolates, likely due to the high tannin and flavonoid content (Table 1). e test strains were shown to have antibacterial activity. e highest spectrum activity was seen against S. mutans and Bacillus subtilis at a low dosage of 1.25 mg/mL. (l4&l2 mm) [18]. Above all, our research indicates that the seed possessed antimicrobial properties. According to the findings, consuming the seed in a controlled manner may help to prevent bacterial infections in the intestine (Table 1). According to the review, the antibacterial potentials of plant extracts have been widely investigated (Table 1). e ethnobotanical research showing the traditional therapeutic potential of plant parts were confirmed in this review. According to the reported research in the following studies, all extracts tested against the tested bacterial strains, whether from human, animal, or other sources, strongly inhibited growth at a high inhibition zone (Table 1).

Antifungal.
e utilization of plant extracts as sources for developing novel antifungal medicines has long been practiced. Plant-based medicines have considerably enhanced human health and well-being. e extracts also had antifungal efficacy against Aspergillus niger. Compared to the standard antibiotics used in the investigation, the data show that the compound has substantial antifungal properties [19]. In a fungistatic approach, the seed extract exhibits high action against Candida albicans and Aspergillus flavus (Table 1). e MICs of ketoconazole [standard medications], which had a range of 275-691/mL and 346-318/mL, respectively, the fungus ranged from 275-691/mL and 346-318/mL. ese findings suggest that the extract may include compounds that can combat microbial illness [20].

Antiviral.
is research has found that the extract's ability to immediately remedy a patient's ocular symptoms and indicators is obvious and encouraging (Table 1). Given the lack of a particular antiadenoviral medication on the market, this could be a game-changer in treating these viral infections [21]. According to this study, G kola is effective against viral infection and in areas where resources are scarce (Table 1).

Antihypertension.
Hypertension, well-known as high blood pressure, is considered by persistently excessive blood pressure in the arteries [22]. High blood pressure can damage arteries supplying blood to the kidneys, heart, brain, and eyes [22]. e blood pressure of rats fed G kola enriched meals dropped significantly by the third week at p < 0.05. Finally, G. kola contains a vasoactive component that can reduce blood pressure. However, the actual method of action is still unknown (Table 1). Traditional medicinal practitioners have always advocated for using G. kola parts to treat hypertension. e findings of the following studies bring up new research options for new antihypertensive drugs or herbal formulations. Plant-based treatments are considered effective.

Anti-Inflammatory.
Inflammation is the body's natural response to damage or foreign irritation. Inflammation, marked by pain, has been known to humanity since the dawn of time. Since the dawn of time, humans have been looking for ways to reduce and manage inflammation, including using plants [1]. Treatment with 25, 50, and 100 g/ mL inhibited cell proliferation in a dosage and time-dependent approach. e inclusion of chemicals with antiinflammatory characteristics contributed to the study's findings [23]. It could be beneficial in conditions marked by cellular proliferation and inflammatory reactions [24].
3.9. Antidiabetic. Diabetes mellitus is a metabolic condition characterized by hyperglycemia, the most prevalent symptom. Its chronic stage impacts blood vessels, kidneys, the heart, and nerves [25]. Diabetes affects 463 million people worldwide, and that number is expected to rise to 578 million by 2030 [25]. At a dose of 100 mg·kg 1 , kolaviron linked bioflavonoids effectively reduced hypoglycemic symptoms in normal and alloxan diabetic rabbits (Table 1). Compared to the controls, there was no significant change (p > 0.05) in single-dose glucose levels, long-term HDL levels, or body weight. However, glucose (mmol/L) levels in the four-week treated rats were significantly lower (16.22.9; p > 00.05) than in the controls (21.63.6), and LDL levels were 66% lower in the treated group (p < 0.01; 86.818.2 against 29.810.9) ( Table 1). On day 7, the 500 mg/kg ethanolic seeds extract-treated group had a 49.70% drop in blood glucose levels compared to the positive control group (45.03%). e findings of this investigation suggested that the seed could be used to treat illnesses and diabetic management [26]. e results mentioned above validate the usage of the plants in the traditional medicinal system to treat diabetes by traditional practitioners.
3.10. Antianalgesic. Controlling acute and chronic pain has become a serious concern, particularly among the elderly. Pain is a nonspecific symptom of many diseases that lead to unpleasant emotional and sensory experiences. e findings show that the chemical possesses dose-dependent antinociceptive properties against acetic acid-induced abdominal constriction in mice (Table 1). At all doses, there was a reduction in the number of writhes compared to control animals at p < 0.05. e seed has antianalgesic properties [27]. e studies examined in the following study found the extract from bitter kola exhibited strong antianalgesic properties.
3.11. Antipneumonia. Pneumonia is an inflammatory, infectious lung disease condition that affects the mucosal parts of the lungs and can be acute and persistent [28]. Fungi, bacteria, and viruses cause the disorder. Anti-Klebsiella pneumonia activity rose when kolaviron concentrations dropped. Kolaviron was efficacious at 500 mg/kg and showed a significant difference at p < 0.0001. Bitter kola can treat pneumonia because it contains antimicrobial properties (Table 1). Advances in Pharmacological and Pharmaceutical Sciences

Seeds
In flies fed a diet enriched with higher G. kola seed inclusions, GST and catalase activities were dramatically boosted, whereas NO content was significantly reduced compared to controls. [42] In vivo

Seed
Petroleum ether Kolaviron appears to operate as an in vivo natural antioxidant and an effective hepatoprotective agent in the current investigation. It is as effective as BHA. [12] In vivo

Seeds
Ethanol ese findings showed that seeds could be useful by reducing the oxidative damage produced by chronic ethanol treatment in Wistar rats' livers.
[ 43] In vivo Seed Methanol Significant rise in total white blood cell count with no increase in hemoglobin at p > 0.05. ese findings imply that the seeds have immune-stimulatory properties, which could support ethno-medicinal efficacy claims. Seed Ethanol is discovery suggested that the extracts may include antioxidants and hence can scavenge free radicals, thereby preventing oxidative stress. is may support their use in treating hepatic dysfunction and stress-related disorders on a local level. [47] In vivo and in vitro

Root
According to the biological evaluation, the saponin extract from the root has scavenging actions against free radicals. e root has the potential to be used as a natural antioxidant source. [48] Seeds Methanol e ME4 had the highest level of activity. e ME4 fraction was also significantly reduced nitric oxide generation in lipopolysaccharide-activated macrophage U937 cells. [49]

In vivo
Leaf Cold 70% ethanol e extract inhibits the most in both liver and brain homogenates at the same concentration (26.7 g/mL), with the percent inhibition of 64.1% and 38.25, respectively.

Aqueous and ethanol
At p > 0.05, the ethanolic extract had considerably better characteristics. Given this, the usage of the plant in traditional medicines for the treatment of cough and liver diseases could be linked to its phytochemical composition. [50] DPPH, FRAP Seeds Aqueous It exhibited significant antioxidant activity at varying doses, which might be attributed to diverse phenolic components in the plants. [51] In Vivo Seeds Compared to the control group, prolonged administration had no negative effects on spermatozoa features but considerably increased testosterone concentration.
Malondialdehyde levels in the liver, testes, and spermatozoa of rats were much lower as antioxidant systems improved.
When compared to controls, prolonged administration of G. kola had no effect on the liver and testes at all doses, according to histological analysis. [52] e antioxidant regarding the phenolic content was found between 10-21 mg·g −1 . e scavenging at 26%-55% was high, showing that it could be a good source of natural antioxidants and employed as food supplements. [13] DPPH Seed oil n-hexane e highest scavenging activity was recorded at 91.05 ± 0.12 mg/mL. [53] DPPH Seed Ethanol e antioxidant studies revealed a dose-dependent substantial (p > 0.05) increase in its ability to scavenge free radicals. e findings of this investigation suggested that the seed could be used to treat free radical-mediated illnesses. [26] In vivo Seed Ethanol On day 7, the 500 mg/kg extract-treated group had a 49.70% drop in blood glucose levels compared to the positive control group (45.03%). e findings of this investigation suggested that the seed could be used to treat illnesses and diabetic management. [26] Linoleic acid system Seed Petroleum ether Seeds overall antioxidant activity on lipid peroxidation might be ascribed to their ability to scavenge free radicals and active oxygen species. It could be linked to the inhibition of in vivo lipid peroxidation propagation. [54] In vivo

Seed
Ethanol When compared to rats in group 2, the glutathione concentration of the group was significantly lower (p < 0.05). Compared to rats in group 1 and the treatment group, the vitamin C level in group 2 was significantly lower (p < 0.05). [55] 2 Agar well diffusion Seeds Acetone e synergistic efficacy of bitter kola and fantastic kola exhibited superior antibacterial activities. e positive results for both Gram negative (Escherichia coli, Pseudomonas sp.) and Gram-positive (S. aureus and Bacillus sp.) bacteria indicate that they could be employed as broad-spectrum antibiotics. [56] Agar well diffusion Ethan, aqueous At a 30 mg/mL of ethanol and aqueous (hot water) dosage, extracts showed higher antibacterial activity, with zones of inhibition ranging from 17 to 23 mm for ethanol. [19] Agar dilution method Seed Methanol and aqueous is study found that G. kola extracts have good antifungal activity against clinical isolates of Fusobacterium nucleatum and its connection with periodontal infections. [57] Seed Ethanol e extract was the most effective against the test organisms, with a mean inhibition zone of 15.33 mm. As a result, it can be deduced that bitter kola, kola nut, and avocado seeds exhibit antibacterial action, with the kind of extracting solvent having a significant impact on the level of antimicrobial activity.
is means that an antibacterial seed or herb extract should be made in the most appropriate solvent for maximum efficiency. [58] Disc diffusion method Leaf Methanol and aqueous e extracts ranged from 25 mgL −1 to 50 mgL −1 . e findings suggest that these plants' leaves could be utilized to treat ailments caused by the test organisms. e bioactive components of the leaves would be characterised further using crude extracts. [59] Agar-well diffusion method Seed Methanol At a 20 mg/mL final dosage, the extract showed considerable inhibitory effect against all examined bacteria except four. e inhibition zones varied from 10 to 23 mm, while the typical antibiotics' zones of inhibition ranged from 15 to 25 mm; 12 and 25 mm, respectively. [60] Tube dilution susceptibility Leaves (combine with other plants) Aqueous e findings imply that the formulation has high in vitro antibacterial activity against common wound isolates and could be used for routine wound and sepsis treatment instead of antibiotic chemotherapy. [61] In Vivo Seed n-hexane, hot aqueous and ethanol e best antibacterial activity was found in the n-hexane extract, followed by ethanol and finally hot water. According to MIC, the inhibitory zone diameter of n-hexane clove extract was the biggest, followed by bitter kola extract, and finally tobacco extract. [62] Test tubes bottles Seed oil n-hexane e oil was discovered to have broad-spectrum activity against gram-positive and gram-negative bacteria isolates, which was concentration-dependent. [63] Agar-well diffusion method Seeds Methanol, aqueous At the same dose of 2.5 mg/mL, the extract had bactericidal activity against Klebsiella pneumoniae and Shigella species. As a result, pharmaceutical companies should examine extracts that have been demonstrated to be effective against test organisms. [64]

In vivo
Seed Aqueous e findings show that both uncoated and coated bitter cola has medical promise as a lead toxicity reducer and alternative antibacterial. Furthermore, it could be a two-edged sword for treating lead toxicity and subsequent infections caused by lead poisoning. [15] Microdilution broth method Leaf (EO) e oil contains several chemicals that were active against the bacteria tested, with minimum inhibitory concentrations ranging from 50 to 400 g/mL and might be used to produce plant-based medications. [65] Agar diffusion method Seeds Petroleum ether, 70% ethanol and aqueous e presence of a polyisoprenyl benzophenone (Kolanone) in the petroleum ether extract and the hydroxy biflavanonols in the ethyl acetate fraction was found to be responsible for the observed activity. [66] MIC Seed Ethanol e extract had a broad spectrum of activity, whereas the fractions had a narrow spectrum of activity because they were only active against S. aureus, E. coli, and Pseudomonas aeruginosa. ese findings could explain why G. kola seeds are useful in treating microbial diseases. [67] Methanol Compared to chloramphenicol [standard medicine], which had MICs of 14.31-31.62 g/mL, the minimum inhibitory concentration (MIC) for bacteria. [20] Agar disc diffusion method Seed Aqueous As a result, the findings imply that biogenic AgNPs have potential biological applications and might potentially be used as a key component in the development of innovative nanopaints against the tested bacterial strains. [68] Disc diffusion Seed Aqueous, ethanol and methanol is study reveals that seeds extracts from these plants have antibacterial characteristics and could be utilized as an alternative to antibiotics. [69] Checkerboard technique Seeds Methanol e extract's MICs against microorganisms were found to be 1.562 and 3.125 mg/mL, respectively. [70] Disk Seeds e ethanol seeds extract was found to have significantly higher activity (p < 0.001) than the aqueous preparation. e presence of several pharmacokinetic substances could explain the activity. [71] Agar-well diffusion method Seeds (black nanocrystal of silver nanoparticles)

Aqueous
All of the bacteria examined showed that the produced silver had good antibacterial action. Green nanoparticles can be employed in a variety of medicinal applications. [72] Agar diffusion method Seed Methanol and aqueous ere was a higher level of activity with the hot water seeds extract. e findings supported herbalists' historical usage of botanicals in treating bacterial illnesses. [73] Agar-well diffusion method Seed Petroleum ether Antimicrobial activity against a broad spectrum of microorganisms has been observed in the isolated chemical. [74] Disc Seeds Aqueous and ethanol At p < 0.05, the results were significant. Against the bacterial isolates, the extracts demonstrated different levels of inhibition. [75] Disk Seeds Aqueous and ethanol At p < 0.05, the results were significant. Against the fungal isolates, the extracts demonstrated different levels of inhibition. [75] Agar-well diffusion method Leaves Cold aqueous, hot aqueous, ethanol and methanol e MIC was evaluated at different concentrations of 25 and 12.5 mg/mL and showed efficacy. e findings support the plant's long-standing use in Nigerian rural communities to treat infectious disorders. [76] Agar well diffusion Seeds Methanol, chloroform, and ethyl acetate Antibacterial activity was found in the plant seed extracts against the test strains. However, at a low dose of 1.25 mg/mL, the maximum spectrum activity was observed against S. mutans and B. subtilis (l4 and l2 mm). e findings suggested that using these plant extracts as nutraceuticals could help to minimize the risk of microbial infections. [18] Agar well diffusion Seeds 100% (neat) With a zone diameter of 22.0 mm and above, the extract showed significant inhibition against the strains. We infer that the seed extract could be a source of broad-spectrum antibiotic resistance-modifying chemicals. [79] Disc diffusion Seed Ethanol (70%) e extracts showed an inhibitory effect on the test isolates, likely due to the high tannin and flavonoid content. Above all, our research indicates that the seed possessed antimicrobial properties. According to the findings, consuming the seed in a controlled manner may help to prevent bacterial infections in the intestine. [16] Agar well diffusion Seed Ethanol and aqueous e effects of various concentrations were studied. It was discovered that a synergistic blend of aqueous and honey seed extracts was more effective than using the extracts separately in suppressing the growth of the bacterial strain. [80] Disc Seeds Petroleum ether, acetone and ethanol Antibacterial sensitivity testing revealed that the extracts reduced the growth of the test isolates, as evidenced by measured zones of inhibition, which differed between species. [46] Ager well Seeds Ethyl acetate, ethanol, methanol, acetone and aqueous e extracts had inhibitory zone widths ranging from 0-24 1.1 mm, with MIC and MBC values of 0.04-1.25 mg/mL and 0.081-2.5 mg/mL, respectively. e findings of this study support the use of this plant in traditional medicine and provide a lead for the creation of new and powerful antimicrobials. [81] Bottles of molten agar Seeds Methanol e antibacterial activity against all isolates was significantly lower than the standard antibiotic, gentamicin 4 mg/mL, at p > 0.05. Similarly, the activity was dose-dependent, with greater inhibition zones corresponding to higher concentrations at p > 0.05. [82] In vivo Seeds Aqueous At 1 and 2.5 h, the interaction was antagonistic, but at 4 h, it became potentiated. e actual mechanism that causes the observed biphasic interaction is unknown. [83] Agar diffusion method Seeds Aqueous, ethanol, and methanol e crude extracts' sensitivity patterns of inhibition zones revealed a proportionate degree of inhibitory activity against the tested bacterial strain. [84] Agar well diffusion Seeds Ethanol e findings of this investigation revealed that the extract had inhibitory activity against the bacterial isolates tested at various concentrations, with a greater inhibitory effect on E. coli at a concentration of 300 mg/mL shows that as the concentration of the extract against the bacteria increases, the zones of inhibition expand. [85] Cup plate method and broth dilution Disc Bark Aqueous e antibacterial screening of the biosynthesised AgNPs revealed that they had inhibitory potential and could hinder microorganisms' growth. [93] Tube dilution Leaves Aqueous e findings imply that the formulation has high in vitro antibacterial activity against common wound isolates and could be used for routine wound and sepsis treatment instead of antibiotics and chemotherapy. [94] Agar well method

Bark and seeds
Ethanol e extract inhibited all tested bacterial strains in a zone of inhibition ranging from 12 to 23 mm. [95] Agar well diffusion More research is needed to determine the sort of antimicrobial activity they exhibit (bactericidal or bacteriostatic), as well as the active components contained in the vinegar samples that allow them to exhibit such activities. [96] Disc Seed Ethanol Antibacterial activity tests revealed that all three eluates had cumulative bactericidal activity against five of the ten species tested. e pyridine/pyrimidine moiety in Eluate 2 suppressed the development of K. aerogenes in a way that the other eluates and the broad-spectrum antibiotic levofloxacin did not. [97] Agar diffusion method Seeds Aqueous and ethanol e various test plant extracts moderately inhibited the standard bacteria E. coli NCTC 10418 and S. aureus NCTC 6571, with inhibition zones ranging from 8 mm to 20 mm. e antibacterial properties of these plants are revealed in this investigation. [98] Agar well diffusion method Seeds Methanol e extract exhibited strong activity against the tested strains. [99] Agar diffusion Seed oil n-hexane Antibacterial tests revealed a high susceptibility to all germs examined. Salmonella typhi was the most susceptible of the bacteria tested, with an inhibition of 27 mm, while E. coli had the least, with an inhibition of 12 mm, at a dose of 100 mg/mL. [53] Polyphenolic IR, 1H, and 13C-NMR spectroscopy were used to characterize the fraction with the strongest antibacterial potential. e molecule could be Catechin, methyl-dl-tyrosine, p-naphtholbenzein-or Naringin, according to the combined spectroscopic data. [100] Agar well diffusion Leaves Ethanol, methanol, hot and cold aqueous e findings revealed that of the 96 wound swabs collected, 15 (21.7%) bacteria pathogens were identified in the following order: E. coli 9 (60%), P. aeruginosa 4 (26.6%), Klebsiella spp 1 (6.6%), and S. aureus 1 (6.6%). [101] Agar well diffusion Seeds Methanol, ethanol, and aqueous Methanolic and ethanolic seed extracts were found to have antibacterial action against gram-positive and gram-negative bacteria. [102] 4 Advances in Pharmacological and Pharmaceutical Sciences  [20] Microdilution broth method Leaf (essential oil) e oil contains several chemicals that were active against the fungi tested, with minimum inhibitory concentrations ranging from >400 to 50 g/mL and might be used to produce plant-based medications.
[ 65] In vivo Seed Aqueous According to this study, seeds of G. kola are good against candida infection. In resource-constrained regions. [104] Agar-well diffusion method Seeds (black nanocrystal of silver nanoparticles) Aqueous e fungal examined showed that the produced silver had good antibacterial action. Green nanoparticles can be employed in a variety of medicinal applications. [72] Agar Disc diffusion method Seed Aqueous As a result, the findings imply that biogenic AgNPs have potential biological applications and might potentially be used as a key component in the development of innovative nanopaint against the tested fungal strains. [68] Disc Seeds C. albicans had no response to various concentrations used in the water extract. e ethanol extract was found to have significantly higher activity (p > 0.001) than the aqueous preparation. e presence of several pharmacokinetic substances could explain the activity. [71] Agar well diffusion Seeds Ethanol On the fungal isolates, the extract has no inhibitory effect. [85] Checkerboard assay Seeds Ethanol In comparison to their separate activities, the combined activities of the two extracts demonstrated a significant improvement in anti-Candida activity. e findings suggest using the ethanolic seeds extracts' with individual bioactive ingredients and combining them to create viable antifungal medicines. [105] 5 Antiviral

In vivo
Aqueous is research has found that the extract's ability to immediately remedy the patient's ocular symptoms and indicators is obvious and encouraging. [21] 5 Antihypertension

In vivo
Chloroform, methanol In the third week, rats fed G. kola enriched diet showed a significant drop in blood pressure (p > 0.05). Finally, Garcinia kola includes a vasoactive component that can help to decrease blood pressure.
However, the exact mechanism of action is still unknown.
[ 106] In vivo After histaminergic blockage, however, there was a substantial (p < 0.05) decrease in the extract effect. According to this study, the alcohol extract of G. kola has a vasoactive component that lowers blood pressure. [107] In vivo e intraocular pressure of healthy young people was reduced by 21% after taking it orally. Patients with POAG or ocular hypertension in low-income settings may benefit from this effect. [34] 6 Anti-inflammatory

In vivo
Seed When compared to aspirin, the anti-inflammatory potency of acetylsalicylic acid demonstrated rather good anti-inflammatory action. e greatest edema inhibition achieved in rats pretreated with 100 mg/kg kolaviron (59.52% ± 4.65) is comparable to that obtained with 150 mg/kg Aspirin (62.05 ± %3.75). [108] Cell proliferation assay Seed G kola seeds appears to have the capacity to reduce mitogen-activated vascular cell proliferation as well as inflammatory responses. [24] In vivo Seed 70% methanol In albino Wistar rats, the extract at dosages of 500, 1000, and 1500 mg/kg exhibited a statistically significant (p < 0.01) dose-dependent decrease of brewer's yeast-induced pyrexia. e findings reveal that the extracts had a strong antipyretic effect, indicating that their ethnomedicinal use is justified. [109] In vivo Seeds G. kola seeds appeared to provide clinically significant analgesic/anti-inflammatory benefits in knee osteoarthritis patients. [110] MTT assay Seeds Methanol Treatment with 25, 50, and 100 g/mL inhibited cell proliferation in a dose-and time-dependent manner. e inclusion of chemicals with anti-inflammatory characteristics contributed to the study's findings [23] 7 Antidiabetic

In vivo
Seeds Ethanol Compared to the controls, there was no significant difference (p > 0.05) in single-dose glucose levels, long-term HDL levels, or body weights. However, glucose (mmol/L) levels in the four-week treated rats were considerably lower ( [111]

In vivo
Kolaviron At a dose of 100 mg kg 1 , kolaviron-linked biflavonoids effectively reduced hypoglycemic symptoms in normal and alloxan diabetic rabbits. [112] 8 Analgesic

In vivo
Seeds Ethanol At all doses, there was a reduction in the number of writhes compared to control animals at p < 0.05. e seed has antianalgesic properties. [27] In vivo Seed e findings reveal that the chemical has antinociceptive activity against acetic acid-induced abdominal constriction in mice in a dose-dependent manner. [108] 9 Antipneumonia Seeds With a drop in the concentration of seeds, anti-Klebsiella pneumonia activity increased. e seed was effective at 500 mg/kg and exhibited significance at p < 0.0001. [28] 10 Antiobesity

In vivo
Seeds Ethanol e results revealed a considerable rise in the counts of RBCS in both tested animals, as well as a reduction in their weight. Very low-level density lipoprotein in the plasma was reduced in the dependent-dose approach, while the level of chylomicrons increased in a dependent-dose approach. Low levels of high-density lipoproteins and an increase in low-density lipoproteins play a role in cardiovascular disease. [113] 11

Fertility evaluation
In vivo Seeds For 28 days, animals were grouped into 4. 100, 200, and 400 mg/kg body extracts were given in groups 2, 3, and 4, respectively. A solution of normal saline was given to the control group.
When comparing serum levels of LH and testosterone in rats treated with bitter kola extract to those in the control group, a dose-dependent drop was detected at p < 0.05. On the other hand, the extract did not affect FSH levels in the blood at any of the amounts tested. is finding revealed that bitter kola could lower fertility in male Wistar rats. [33]

In vivo
Ethanol Experimental models were grouped into three: groups 1 and 2 were given extracts orally at doses of 400 and 200 mg for 28 days, respectively, while group 3 was the control.
Group 1 exhibited modest interstitial congestion, disorientation of the cells, whereas group 2 had a normal interstitial space with the regeneration of the germinal epithelium and a small number of matured spermatozoa, according to the study. As a result, this research implies that excessive intake may have a more negative impact on sperm parameters and testis shape. [32] In vivo Seed Ethanol e extract has been shown to have an antispermatogenic effect in male Wistar rats. It may be harmful to male reproductive health, necessitating managing its intake rate. [114] In vivo

Seed Aqueous
In a dose-dependent manner, the extract reduced sperm motility, concentration, and viability and affected normal sperm cell morphology. [115]

In vitro
Seeds Methanol e seeds extract had dose-dependent effects on induced cholinergic contractions and spasms generated by cumulatively raised concentrations of barium chloride and acetylcholine. [116] 12 Antitrypanosoma

In vivo
Seeds 50 and 100% and methanol Except for the group given 600 mg/kg body weight per day of 50% of the extract, which had a very low parasite count for nearly four months after treatment was terminated, but all treated died.

In vivo
Seeds Ethanol e findings revealed erythrocyte count, PCV, and hemoglobin concentration values had all reduced dramatically. is demonstrates that it is an active ingredient and has no long-term toxicological implications when tested on mammalian erythrocytes. [118] 14 Geotactic behavior

Seeds
In flies fed a diet enriched with higher G kola seed inclusions, GST and catalase activities were dramatically boosted, whereas NO content was significantly reduced compared to controls. [42] 15

In vivo
Seed 70% Ethanol ese findings suggest that they play a role in regulating cortisol, potassium, and sodium secretion control. Despite the possible benefits, it should be used with caution because it is a depressive. [37] 16 Growth promoter

In vivo
Contain chemicals that reduce feed intake and growth performance. e effect appears to get stronger as the concentration gets higher. However, because the RBC and WBC levels increased, it is recommended that G. kola seeds be used in small doses or sporadically rather than continuously. [119]

In vivo
Seeds e inclusion of G. kola in the feed resulted in the highest feed efficacy. e study found no evidence of mortality. [120]

In vivo
Seeds ere were no variations in the moisture, protein, or ash content of the fish carcasses between the treatments (p > 0.05). e findings imply that feeding C. gariepinus fingerlings G. kola seed powder increased growth rate, feed utilization, and survival. [121]

In vivo
Seed Ethanol e growth parameters and the food conversion ratio showed significant differences at p > 0.05. e fish fed a 1.0 g/kg ethanolic extract diet gained the most weight compared to the other treatments. is supports the probiotic benefits of the plant as a growth promoter. [122]

In vivo
Seeds ere are no differences in any performance indicators assessed between birds treated with BK 5 and those treated with BK 10. Birds on BK 5 showed greater FW, WG, and ADWG (p > 0.05).
At a 5 g/kg diet, sun-dried ground bitter kola could be utilized as a supplement in broiler diets. [123] 17

Liver injury
In vivo 70% ethanol e findings showed that combining the two plants had a therapeutic effect on the wounded liver's repair. is supported its long-standing use in the treatment of liver-infected patients. [124] 18 Haematological evaluation

In vivo
Seed Aqueous ese data imply that it has no negative effects on the liver's activity and may have a favorable effect, as evidenced by its ability to reduce serum total cholesterol content and boost WBC count significantly. [41] In vivo

Seeds Ethanol
As a result, this extract has a minor erythropoietic impact, but a moderate leucopenia characterized by lymphocytosis but a decrease in all other WBC lines.
[ 125] In vivo Seed e result revealed that the meal increases the number of lymphocytes in rabbit bucks, which lead to an increase in total white blood cell count. Serum biochemical features revealed possible modest organ degeneration, as evidenced by a substantial (p > 0.05) increase in aspartate amino transaminase (AST) and alanine amino transaminase (ALT) in rats fed Garcinia kola seed meal diets. [126]

In vivo
Seed Ethanol e extract reduced the volume of the cell, mean cell, and hemoglobin cell mean in the animals' plasma substantially (p > 0.05). As a result of its antioxidant properties, the ethanolic extract of G. kola seed has hematological, stimulating, and boosting effects. [40] In vivo

Seed
Ethanol White blood cells proliferated significantly in this study, with a p > 0.05. Given the critical function that white blood cells play in the body's immune defense mechanism in organisms, this most likely explains the antibacterial activity of ethanolic extracts of plants. [122] 19 Cytotoxicity

In vivo
Seeds Compared to control flies, the high concentration of the plant in the diet dramatically reduced the survival rate of the experimental model. ese findings could be linked to the bioactivity of G. kola seed compounds, including saponins and glycosides, which are hazardous at high concentrations. As a result of this research, it appears that excessive use of G. kola seeds may have toxicological consequences and that moderate consumption is therefore advised. [42] Median lethal dose (LD50)

Stem bark
Methanol e extract did not appear to have any significant toxicological effects on the erythrocytes, although it did exhibit a propensity to increase the number of erythrocytes over time. [127] In vivo Seed CdCl2 dramatically reduced the number of spermatozoa in the seminiferous tubules, resulting in decreased spermatogenesis, sperm counts, and histopathology. [128] In vivo Advances in Pharmacological and Pharmaceutical Sciences 3.12. Antiobesity. Obesity is a complicated health condition classified as a chronic disease that has a detrimental impact on the human body [29]. Obesity raises the risk of diabetes, hypertension, heart disease, and other serious illnesses. Obesity cases are increasing at an alarming rate worldwide [30]. ere are currently more than 300 million obese people on the planet [31]. e results revealed a considerable rise in the counts of RBCS in both tested animals, as well as a reduction in their weight. Very low-level density of lipoprotein in the plasma was reduced in the approach of dependent dose, while the level of chylomicrons increased in a dependent-dose approach. Low levels of high-density lipoproteins and an increase in low-density lipoproteins play a role in cardiovascular diseases (Table 1).

Fertility Evaluation.
Medicinal plants have long been used to boost or manage fertility. e experimental model was divided into three groups: groups 1 and 2 received the extracts orally at doses of 400 and 200 mg for 28 days, respectively, while group 3 served as a control group. According to the study, group 1 had slight interstitial congestion disorientation of the cells, whereas group 2 had a normal interstitial space with germinal epithelium regeneration and a small number of matured spermatozoa. As a result, this study suggests that a high-calorie diet could have a deleterious impact on sperm parameters and testis shape [32]. is discovery demonstrated that bitter kola could reduce fertility in male Wistar rats [33]. e extract has been proven to have an antispermatogenic effect. It can damage the male reproductive organs, necessitating controlling the amount consumed (Table 1).
3.14. Antiglaucoma. Everywhere across the globe, glaucoma is the most common cause of permanent blindness [34]. e most prevalent kind of primary open-angle glaucoma (POAG) is characterized by progressive optic nerve degeneration and affects over 60 million individuals worldwide. In the African continent, 15% of blindness was due to glaucoma [34]. After taking it orally, healthy young people's intraocular pressure was lowered by 21%. In low-income settings, patients with POAG or ocular hypertension may benefit from such an effect (Table 1).

3.15.
Antitrypanosome. Humans and animals are both affected by trypanosomiasis, a parasite disease. Trypanosoma is a parasite species that causes the disease. More than 50 million individuals and more than 50 million animals are infected worldwide [35]. Only the experimental model that received the dose of 600 mg/kg per day of their body weight, which got a very minimal parasite total for nearly four months after therapy, was terminated. Yet, all those who were on it died (Table 1).

Ingestion.
e results revealed that the erythrocyte count, PCV, and hemoglobin concentration had all dropped significantly. When evaluated on mammalian erythrocytes, this shows that the active component has no long-term toxicological effects (Table 1).

Geotactic
Behavior. All living species have an inbuilt behavioral response called geotaxis, defined by motor actions toward or away from the Earth. Flying animals, in particular, have a lot of negative geotaxis against Earth's gravity [36]. In flies fed a diet enriched with higher G. kola seed inclusions, GST, and catalase activities were dramatically boosted, whereas no content was significantly reduced compared to controls (Table 1).

Steroid Hormones.
ese data imply that the seed extract plays a function in cortisol, potassium, and sodium secretion regulation (Table 1). Despite its potential benefits, it should be used with caution because it is a depressive drug [37]. ese data imply that plays a function in cortisol, potassium, and sodium secretion regulation. It should be used with caution because it is a depressant ( Table 1).

Growth Performance.
e moisture, protein, and ash content of the fish carcasses did not differ across the treatments (p > 0.05). e data suggest that feeding G. kola seed powder to Clarias gariepinus fingerlings boosted growth rate, feed utilization, and survival (Table 1). At p > 0.05, there were significant variations in the growth metrics and the food conversion ratio. Compared to the other treatments, the fish given 1.0 g/kg ethanolic seed extract diets gain the most weight. is supports the plant's probiotic advantages as a growth promoter (Table 1).

Healing of Liver Injury.
e liver is a vital organ in our body responsible for most metabolic and secretory functions. As a result, it appears to be a sensitive target for drugs that modulate biotransformation [38]. e duration or persistence of a liver injury is arbitrarily split into acute and chronic liver injury in clinical practice [39]. e researchers discovered that combining the two plants had a therapeutic effect on the healing of the injured liver. is backed up its long-standing usage in treating individuals with liver infections (Table 1). e plant has the potential to be utilized in the development of drugs for liver treatment.
3.21. Hematological Analysis. As a result, the aqueous seed extract has a minimal erythropoietic effect but causes moderate leucopenia with lymphocytosis and a decrease in all other WBC lines (Table 1). e extract significantly decreased the volume of the cell mean cell and hemoglobin cell means in the plasma of the animals (p < 0.05). e ethanolic extract of G kola seed has hematological, stimulating, and enhancing effects due to its antioxidant qualities [40]. ese findings suggest that it has no harmful effects on the liver's function and may have a beneficial effect, as indicated by its capacity to drastically lower total serum cholesterol and increase WBC count [41]. Advances in Pharmacological and Pharmaceutical Sciences    [129]. Parts of medicinal plants are considered the reservoir of a novel compound with a therapeutic potential to treat a wide array of diseases compared to the synthetic drugs available [130]. Many studies have proven that medicinal plants contain a wide array of compounds that have a positive biological effect [8,11]. ese components are only beneficial if they are confirmed to be nontoxic or have minimal toxicity. Quite a number of studies have been carried out on the toxicity of G. kola parts (Table 1) both in vivo and in vitro. Higher dietary intake of G. kola seeds drastically lowered the survival rate of D. melanogaster compared to control flies [42]. ese findings could be linked to the bioactivity of G. kola seed components such saponins and glycosides, both of which are hazardous in large doses. e extract did not appear to have any substantial toxicological effects on erythrocytes, although it did tend to increase erythrocyte amount over time [127]. e results showed that neither medicinal plant extract had any significant negative effects on total protein or glutamate pyruvic transaminase at p > 0.05 compared to the control [86]. Garcinia kola has modest toxicity, with an oral 50% fatal dose of over 5000 mg/kg bw [52]. Based on the study's findings, excessive usage of G. kola seeds may have Advances in Pharmacological and Pharmaceutical Sciences toxicological implications, and moderate use is consequently recommended.

Chemical Compounds Responsible for the Biological
Activity. Due to the presence of tannin in the plant, it could be used to cure burns and wounds [131]. e plant's high alkaloid and flavonoid content suggest that they have antioxidant potential and explain their medicinal activities, which might be exploited in drug formulation [131]. e presence of large levels of flavonoids in all plant parts demonstrated that the plants perform biological tasks such as protecting against allergies, free radicals, microbes, ulcers, inflammation, hepatotoxins, and viruses ( Figure 2). Natural compounds, including garcinoic acid, garcinol, and tocotrienol extracted from the seed of G. kola from Nigeria, have 1.5 times the antioxidant activity of a-tocopherol [52]. e ME4 fraction was chromatographically fractionated and spectroscopically analyzed, revealing the presence of some compounds: Garcinia biflavonoids 1, Garcinol and Garcinoic acid ( Figure 2). ese findings suggest that these four chemicals are responsible for some of G. kola seeds' high antioxidant activity. is adds to the evidence of G. kola's nutraceutical and medicinal potentials [132]. e ability of a plant extract to inhibit bacteria, particularly those with substantial health implications, is mainly dependent on essential phytochemical components having antimicrobial activity [53]. e presence of a wide range of chemicals in extracts from various plant sections has been linked to their pharmacological properties [53]. e following compounds were reported present in the essential oil extracted from the seed 9-Octadecenoic acid methyl ester, 9,12-Octadecadienoic acid (Z, Z), Stearic acid methyl ester, and Hexadecanoic acid methyl ester; they are reported to be responsible for antibacterial, antioxidant, and many more pharmacological properties ( Figure 2). Research uncovered G. kola was discovered to possess numerous chemical components that have antioxidant properties [133]. Benzophenones, flavonoids, and xanthenes are among the components found in G. kola (Figure 2).
ey are known to have antiparasitic, antiinflammation, antibacterial, and antiviral activities [110]. e anti-inflammatory action of the seed is considered due to the presence of flavonoids and benzophenone [134].

Conclusion and Future Recommendations
Research into the pharmacological benefits of medicinal plants provides us with critical knowledge for better organizing current and future studies to address a variety of human illnesses. G. kola is a remarkable medicinal plant with a variety of traditional usage that has been documented since antiquity. Preclinical investigations have already been conducted on a variety of biological activities. e seeds were found to have significant biological activity, and this is due to the G. kola containing nutritionally and pharmacologically essential compounds. Research into the mechanisms behind the bioactivity of the constituent chemical components is required. As a result, well-designed clinical trials are recommended to obtain more conclusive evidence about the usefulness of G. kola seeds.

Data Availability
Data are available within the manuscript.

Conflicts of Interest
e authors declare that they have no conflicts of interest.